Table 2.

Dynamic contrast-enhanced ultrasound and liver diseases

Ref.	Study design/number of patients	Object of D-CEUS	Population/groups	Machine/UCA/software	Significant results (P < 0.05)
Wildner et al[31], 2022	Prospective/17	Melanoma liver metastasis	Patients with melanoma liver metastasis treated with sorafenib/Responders’ vs non-responders	Sequoia 512/SonoVue/Qontrast	Increase of MTT and TTP is associated with response to treatment and prognosis
Gu et al[30], 2022	Retrospective/97	HCC	Patients with HCC underwent thermal ablation	Acuson Sequoia, Phillip EpiQ7/SonoVue/VueBox	WiAUC, WoAUC, and WiWoAUC ratios between HCC and surrounding parenchyma before ablation were predictors of survival
Huang et al[18], 2022	Prospective/120	HCC	Patients with HCC underwent biopsy/Low-Ki-67 vs high-Ki-67	Logiq E9/Sonazoid/NovoUltrasound Kit	PE difference between HCC and distal liver parenchyma was different in the Kupffer phase
Li et al[22], 2022	Retrospective/31	HCC	Patients with HCC underwent surgery/MVI-positive vs MVI-negative	Phillip EpiQ7/Sonazoid/built-in auto contrast software	None of the D-CEUS parameters was related to MVI
Zocco et al[28], 2013	Prospective/46	Liver parenchyma	Cirrhotic patient underwent HVPG/clinically significant portal hypertension vs severe portal hypertension	iU22/SonoVue/QLAB	Negative correlation between PI, Pw and HVPG. Positive correlation with MTT. AUROC of 1.00 for PI < 23.3 AIU to predict clinically significant portal hypertension
Dong et al[21], 2021	Retrospective/16	HCC	Patients with HCC underwent surgery/MVI-positive vs MVI-negative	Acuson Oxana, Logiq E9, Siemens Acuson Sequoia/SonoVue, Lumason/VueBox	WiAUC and WoAUC were higher in MVI positive group
Schwarz et al[24], 2021	Retrospective/139	Focal liver lesion	Patients with diagnosed focal liver lesion/malignant versus benign	Acuson Sequoia, S2000 or S3000 and Phillip EpiQ7/SonoVue/VueBox	RT and late phase ratio were different between malignant and benign liver lesion
Xuan et al[19], 2021	Retrospective/128	HCC	Patients with HCC underwent biopsy or surgery/highly-differentiated vs moderate-differentiated vs poorly-differentiated	-/SonoVue/-	RT and MTT increased from poorly- to moderate- to highly-differentiated. Enhancement rates decreased from poorly- to moderate- to highly-differentiated
Amadori et al[32], 2018	Prospective/37	CRC Liver metastasis	Patients underwent chemotherapy/chemotherapy vs chemotherapy plus bevacizumab	iU22 vision 2008/SonoVue/QLAB	Reduction of PI and AUC and increase of TPI correlated with higher PFS in chemotherapy plus bevacizumab group
Wildner et al[25], 2019	Prospective/148	Focal liver lesion	Patients with focal liver lesion and subsequent final diagnosis/HCC, CCC, PCA, CRC, BC, MM, FNH	Sequoia 512/SonoVue/VueBox	Higher PE and WiWoAUC in HCC than CRC. Lower Relative intensity signal for PCA and CRC compared to HCC at 30 and 120 s after PE
Mogensen et al[33], 2017	Prospective/12	CRC liver metastasis	Patients underwent chemotherapy/chemotherapy vs chemotherapy plus bevacizumab	Logiq E9/SonoVue/VueBox	Early changes of PE correlate with tumor shrinkage at CT scan
Zocco et al[28], 2013	Prospective/28	HCC	Patients treated with sorafenib/Responders’ vs non-responders	iU22/SonoVue/QLAB	PI, Pw and AUC 10% decrease correlate with response to therapy. AUC 10% decrease and increased/unchanged TPI and MTT are associated with longer survival. Decrease of Pw is associated with PFS
Zhan et al[20], 2019	Prospective/35	HCC	Patients with HCC underwent microwaves ablation	Acuson Sequia/Sonovue/SonoLiver	Positive correlation between MVD, VEGF and IMAX; negative correlation between MVD and TTP. TTP was an independent predictor of OS
Wildner et al[26], 2014	Prospective/43	HCC, ICC	Patient with proven HCC and ICC	Acuson Sequoia 512/SonoVue/VueBox	FT and MTT were lower in ICC than HCC. Relative signal intensity was lower in ICC than HCC in all time point after PE
Frampas et al[69], 2013	Prospective/19	HCC	Patients with HCC treated with sorafenib or sunitinib/RECIST progressor vs non-progressor	Aplio XV/SonoVue/Vascular Recognition Imaging” mode	AUC decrease ≥ 40% correlated with RECIST non-progression
Lassau et al[29], 2011	Prospective/42	HCC	Patients with HCC treated with Bevacizumab	Aplio scanner/SonoVue/Contrast Harmonic Imaging-Quantification software	AUC, WiAUC, WoAUC and TPI decrease correlate with tumor response. TPI decrese correlate with PFS. AUC and WoAC decrease correlate with OS

AIU: Arbitrary intensity unit; AUC: Area under the curve; AUROC: Area under the receiver operating characteristic; BC: Breast cancer; CCC: Cholangiocarcinoma; CRC: Colorectal cancer; CT: Computed tomography; D-CEUS: Dynamic contrast-enhanced ultrasound; FNH: Focal nodular hyperplasia; HCC: Hepatocellular carcinoma; HVPG: Hepatic vein portal pressure; MM: Malignant melanoma; MTT: Mean transit time; MVD: Microvascular density; MVI: Microvascular invasion; OS: Overall survival; PCA: Pancreatic adenocarcinoma; PE: Peak enhancement; PFS: Progression free survival; PI: Peak intensity; Pw: Slope coefficient of wash-in; RECIST: Response evaluation criteria in solid tumors; RT: Rise time; TPI: Time to peak intensity; TTP: Time to peak; UCA: Ultrasound contrast agent; WiAUC: Wash-in area under the curve; WoAUC: Wash-out area under the curve; WiWoAUC: Wash-in and wash-out area under the curve.